“
STEM CELL THERAPY
”
-A REVIEW
Shefali Barkat Dobani*1, Ameesh Shukla1, Dr. Vanita Kanase2, Dr. Pramila Yadav3
1*,1
Oriental College of Pharmacy, Sector 2, Behind Sanpada Railway Station, Sanpada West,
Navi Mumbai, Maharashtra 400705.
2
HOD Pharmacology, Oriental College of Pharmacy, Sector 2, Behind Sanpada Railway
Station, Sanpada West, Navi Mumbai, Maharashtra 400705.
3
Professor in Pharmacology, Dr. D. Y. Patil Medical College, Nerul, Navi Mumbai,
Maharashtra 400614.
ABSTRACT
The regeneration of a lost tissue is known to mankind for several years.
The research on regenerative medicine has gained momentum in the
field of molecular biology. Stem cells have been successfully isolated
from variety of human tissues. Initial evidence from pioneering studies
has documented that stem cells are used for various life-threatening
diseases that have so far defeated modern medical care. The growing
understanding of biological concepts in the regeneration of human
tissues coupled with experiments on stem cells is likely to result in a
paradigm shift in the therapeutic medicines. This review focuses on the
origin of stem cells, their types, their properties, characteristics, their
potential applications, therapies for various diseases and recent
advances in the stem cell therapy.
KEYWORDS: Stem cell, pluripotent, self renewal, differentiation, stem cell therapy for diabetes, cancer, arthritis, Parkinson’s and Alzheimer’s disease.
INTRODUCTION
Stem cells are the body’s natural reservoir – replenishing stocks of specialized cells that have been used up or damaged. Inside one’s bone marrow, stem cells make 100,000 million new
blood cells one needs every single day. Stem cells have the unique ability to produce both
copies of themselves (self-renewal) and other more specialized cell types (differentiation)
every time they divide. Stem cells, therefore, are essential to the maintenance of tissues such
Volume 5, Issue 5, 437-450. Review Article ISSN 2277– 7105
*Corresponding Author Shefali Barkat Dobani Oriental College of
Pharmacy, Sector 2,
Behind Sanpada Railway
Station, Sanpada West,
Navi Mumbai,
Maharashtra 400705. Article Received on 28 Feb 2016,
Revised on 18March 2016, Accepted on 08 April 2016
as blood, skin, and gut that undergo continuous turnover (cell replacement), and muscle,
which can be built up according to the body's needs and is often damaged during physical
exertion.Stem cells are found in the early embryo, the foetus, placenta, umbilical cord, and in
many different tissues of the body. Recently, stem cells have also been engineered from
somatic cells. They are used in the treatment of many disorders and the research in the
modification of the existing treatment of various genetic disorders is still going on.[1]
TYPES OF STEM CELLS
Various types of stem cells are observed in the human body which are classified as.
1)“TISSUE STEM CELLS” - also sometimes called adult stem cells because each type of adult stem cell produces only a limited set of specialized cells characteristic of a particular
tissue — epidermis, blood, and so on - are derived from or resident in a fetal or adult tissue.
Usually they can only give rise to the cells of that tissue. In some tissues, these cells sustain
turnover and repair throughout life. In adults, tissue-specific stem cells are located throughout
the body. The so- called hematopoetic stem cells in bone marrow and umbilical cord blood,
which make all the different types of blood cells, are the easiest to isolate, and have been
used in therapy for decades as bone marrow transplants for diseases such as leukemia, where
the normal development of blood cells has gone awry. For example, stem cells that are found
in the skin will produce new skin cells, ensuring that old or damaged skin cells are
replenished.[2]
2)“EMBRYONIC STEM CELLS”-These cells are derived from a small group of cells (called the inner cell mass) within the very early embryo. Human embryonic stem cells are
obtained from embryos that are 5-6 days old. At the stage that embryonic stem cells are
derived, the embryo is called blastocyst. Embryonic stem cells are said to be pluripotent –
they are able to form all the different types of cell in the body, including germ cells.[2]
3)“INDUCED PLURIPOTENT STEM CELLS”- Recently, a third type of stem cell, with
properties similar to embryonic stem cells, has emerged. Scientists have engineered these
induced pluripotent stem cells (iPS cells) by manipulating the expression of certain genes -
STEM CELL BANKING
Stem cells which is obtained from cord blood can be preserved in the banks. Cord blood,
which contains powerful life saving cells called stem cells, comes from a newborn's umbilical
cord and is collected immediately after birth. Once the umbilical cord has been clamped and
cut, the remaining blood in the umbilical cord is drawn into a collection bag. It may be then
tested, frozen and subsequently stored in a cord blood bank for future use for the treatment of
various diseases. Cord blood stem cells have been successfully used in transplant medicine
for more than 20 years. Cord blood has been used to treat many life-threatening diseases
including leukemia, other cancers, blood disorders, metabolic disorders, and immune
diseases.[3]
MEDICAL USES OF STEM CELL THERAPY
Disease and conditions where stem cell treatment is promising or emerging are:[4]
Research
Clinical trials
Neurodegeneration
Brain and spinal cord injury
Blood cell formation
Baldness
Missing teeth
Deafness
Diabetes
Transplantation
Orthopaedics
Infertility
STEM CELL BASED THERAPY
Adult stem cells have been used in pilot studies as potential cell-based therapy for various
diseases. The following stem cell characteristics make them good candidates for cell-based
therapy.
1. Potential to be harvested from patients.
2. High capacity of cell proliferation in culture.
3. Ease of manipulation to replace existing nonfunctional genes via gene splicing methods.
4. Ability to migrate to host target tissues (homing).
5. Ability to integrate into host tissues and interact with the surrounding tissues.[5]
PROCESS OF STEM CELL BASED THERAPY
Stem cells derived from either peripheral blood, cord blood, bone marrow, or any adult tissue
transported in the right medium to the laboratory is centrifuged, trypsinized, and propagated
under ideal conditions and stored in the master cell bank (MCB). The MCB is further
passaged to yield colonies of stem cells, given the right inductive signals using appropriate
growth factors to allow them to differentiate into required cell types. These are injected or
implanted into a patient as cell-based therapy. Homing will ensure that the stem cells reach
the site of injury/tissues. Today, the two common methods of cell delivery are intravenous
using a carrier). The cell encapsulation approach uses a biocompatible, biodegradable
material construct that is seeded with cells and implanted into defects in order to regenerate
the lost tissue.[5]
STEM CELL THERAPY FOR DIABETES
Diabetes mellitus (or diabetes) is a chronic, lifelong condition that affects your body's ability
to use the energy found in food. There are three major types of diabetes: type 1 diabetes, type
2 diabetes, and gestational diabetes. Curative therapy for diabetes mellitus mainly implies
replacement of functional insulin-producing pancreatic cells, with pancreas or islet-cell
transplants[6].
Stem cell therapy for diabetes implies the replacement of diseased or lost cells from progeny
of pluripotent or multipotent cells. Both embryonic stem cells (derived from the inner cell
mass of a blastocyst) and adult stem cells (found in the postnatal organism) have been used to
generate surrogate cells[6] or otherwise restore cell functioning. In isolated pancreatic tissue,
pancreas-resident progenitor cells might give rise to endocrine islet cells.
Human and rodent pancreatic-duct cells[7,8],islet-derived cells[9,10], and exocrine tissue[11]
contain cells that can differentiate towards a pancreatic endocrine phenotype. These tissues,
cultured and differentiated in vitro, have been transplanted and can reverse diabetes mellitus
in rodents. Rodent-liver stem cells and human fetal-liver cells have been differentiated in
vitro into insulin-secreting cells by culture methods and/or introduction of cell-specific genes.
When transplanted, these cells reverse diabetes mellitus in rodents[12]. Cells within liver that
can differentiate into insulin-secreting cells after introduction of ß-cell-specific genes have
also been seen in vivo after adenoviral gene-delivery into rodents that have been rescued
from diabetes for long periods[13,14].
A bone-fide pancreatic stem cell for cell regeneration remains elusive. A genetic-marking
study in mice casts doubt on the existence of any cell progenitor cells and suggests that cells
regenerate only by proliferation of existing cells[15]. In human beings, early immunological
intervention to stop cell destruction during the development of type 1 diabetes mellitus allows
recovery of pancreatic endocrine function[16,17]. This finding might in part be attributable to
recovery in cell mass by recruitment of local pancreatic or extrapancreatic progenitor cells
that differentiate into cells and/or proliferation of remaining cells during protection from
STEM CELL THERAPY FOR COLLAGEN INDUCED ARTHRITIS (CIA)
Collagen-induced arthritis (CIA) is an animal model of rheumatoid arthritis (RA) that is
widely used to address questions of disease pathogenesis and to validate therapeutic
targets. Arthritis is normally induced in mice or rats by immunization with autologous or
heterologous type II collagen in adjuvant.
Mesenchymal stem cells (MSCs) are precursors of tissue of mesenchymal origin, but they
also have the capacity to regulate the immune response by suppressing T and B lymphocyte
proliferation in a non–major histocompatibility complex–restricted manner.
The heterogeneity of the MSC population is reflected by the absence of a unique, specific
molecular marker. MSCs derived from different tissues express developmental markers of
mesenchymal, endothelial, and hematopoietic tissues.[18-20] but they also produce molecules
directly involved in regulation of the immune response, such as the costimulatory molecule
CD28, the inhibitory molecules programmed death ligand 1(PDL-1) and PDL-2 and an array
of different cytokines[21,22]. Through these molecules, MSCs can regulate the immune
response.
A single intraperitoneal injection of allogeneic MSCs given at the moment of immunization
with CII was sufficient to prevent the occurrence of bone and cartilage erosions in the joints
of immunized mice. These are permanent, irreversible lesions corresponding to the recent
characterization of MSCs and their role in hematopoiesis and immune modulation suggests
their potential use for cell therapy most severe grade of disease and are never observed in
engraft and survive long-term in the appropriate target organs[23], contributing to the repair of
injured tissues.[24,25] Their plasticity and capacity to undergo orthodox and unorthodox
differentiation processes allowed the use of MSCs, alone or combined with biomaterials, for
repair of tissues, such as bone[26], heart[27,28], kidney[29], lung[30,31], and brain.[32] However, in
the experiments it was found that MSC viability was not required for their long-term
immunosuppressant action; MSCs were, in fact, detectable in the recipient for no more than
10 days after treatment. During this time lag, they were able to ―educate‖ other cells to inhibit
the pathogenic immune reaction. Current therapy for RA is directed toward diminishing the
inflammatory response and treating the uncontrolled inflammation. To date, it has not been
possible to prevent the disease or to completely arrest the disease process through medical
therapy. However the research results represent an effective new therapeutic approach to
target the pathogenic mechanism of autoimmune arthritis using adult stem cells.[33]
STEM CELL THERAPY FOR CANCER
Cancer, also known as a malignant tumor or malignant neoplasm, is a group of diseases
involving abnormal cell growth with the potential to invade or spread to other parts of the
body.
Numerous studies have indicated that several human cancer types, including those of the
blood, brain, skin, lung, kidneys, gastrointestinal tract, pancreas, liver, ovarian, prostate and
testis cancers, might arise from the malignant transformation of stem cells and their
progenitors into cancer progenitor cells[34-44] .Several in vitro and in vivo studies have been
new therapeutic targets to block the growth and/or survival of the cancer cells. Among them,
the molecular targeting of distinct oncogenic signaling elements, which are activated in the
cancer cells during the progression of numerous cancer, represents a promising strategy for
the development of new chemopreventive treatments and combination therapies against some
aggressive and metastatic cancers. The aberrant expression and/or activity of diverse
hormones, growth factors, cytokines and chemokines (androgens, estrogens, EGF and
TGF-α/EGFR, IGF/IGFR, SHH/SMO, Wnt/β-catenin, Notch, TGF-β and SDF-1/CXCR4) and
tumorigenic signaling elements (telomerase, PI3K/Akt, NF-κB and Myc-1) may contribute to
the sustained growth and survival of stem cells as well as their malignant transformation
during the initiation and cancer progression[45-50] .Therefore, their molecular targeting is of
importance to eliminate cancer progenitor cells, and thereby inducing a complete tumor
regression and cancer remission.
STEM CELL THERAPY FOR PARKINSON’S AND ALZHEIMER’S DISEASE
Parkinson's disease affects the nerve cells in the brain that produce dopamine. Parkinson's
disease symptoms include muscle rigidity, tremors, and changes in speech and gait.
Alzheimer's disease (AD), also known as Alzheimer disease, or just Alzheimer's, accounts for
60% to 70% of cases of dementia. It is a chronic neurodegenerative disease that usually starts
slowly and gets worse over time. The most common early symptom is difficulty in
remembering recent events (short-term memory loss). As the disease advances, symptoms
can include problems with language, disorientation (including easily getting lost), mood
The motor dysfunctions which are associated with Parkinson’s disease result from the
progressive loss of dopaminergic neurons in the substantia nigra pars compacta, a region of
brain that controls muscle movement. Therefore, cell replacement therapy by delivering new
dopaminergic neurons represents a putative strategy for the treatment of this
neurodegenerative disease[51-53].
A high yield of differentiation of the mouse and human ESCs into the midbrain
TH+-dopaminergic neurons has been obtained in vitro in a stromal cell-derived inducing activity
(SDIA) system or by co-culture with PA6 cells. Importantly, these neuron-like cells
expressed the specific markers of dopaminergic neurons, including the dopamine transporter,
aromatic amino acid decarboxylase, and the transcription factors associated with neuronal
and dopaminergic differentiation (Sox1, Nurr1, Ptx3 and Lmx1b). These cells were also
transplantable and a small number survived in the 6-hydroxydopamine (6-OHDA)-treated
mouse or rat striatum. In addition, Alzheimer’s disease which is characterized by regional
neuronal degeneration and synaptic loss and associated with the presence of senile plaques,
also represents a degenerative disorder that could benefit from neural cell delivery in the
CONCLUSION
Stem cells derived from all sources hold immense medical promises. Stem cell therapies have
virtually unlimited medical applications. While there are several barriers that need to be
broken down before this novel therapy can be translated from lab to clinics, it is certain that
the future is going to be exciting for all of us. We have moved on from the surgical model of
care to the medical model and are likely to move onto the biological model of care. The need
of the hour is high-quality research coupled with collaboration between basic scientists and
the clinicians for the advancement and newer approaches for this therapy. Recent
developments in the technique of stem cell isolation and expansion together with advances in
growth factor biology have set a stage for successful stem cell therapy. Stem cell therapy has
proved beneficial for genetic as well as induced disorders and find its application for treating
many diseases. Stem cell therapy has brought in a lot of optimistic hope amongst researchers,
doctors, and the patients who are the chief beneficiary of this innovation.
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